The compound of the above formula (A) (hereinafter referred to briefly as compound (A)) is described in WO 93/21215. Being a neurokinin receptor antagonist, the compound is useful for the therapy of bronchial asthma and chronic bronchitis, among other diseases.
This compound (A) in the finely divided bulk state is apt to undergo agglomeration and caking so that when processed into a powder inhalant, the bulk substance cannot be sufficiently delivered to the target bronchi.
An apparently reasonable approach would be dispersing it in an aerosol propellant for administration. However, when dispersed in an aerosol propellant, compound (A) remains dispersed only for a short while following shaking of the package but soon begins to be segregated from the propellant, with the result that by the time of dispensing for administration the compound (A) will have separated out to a marked extent to frustrate sufficient medication owing to a variation in the administered dose.
The conventional aerosol product employs one or more kinds of liquefied chlorofluorocarbons (hereinafter referred to collectively as CFC) as a propellant and contains a finely divided powder of the active substance dispersed in CFC with the aid of a suitable dispersant.
However, CFC is involved in destruction of the ozonosphere and, in many countries, a total ban on its use is expected to be enforced within this century at earliest. Therefore, as substitute aerosol propellants, the use of liquefied hydrofluoroalkanes (hereinafter referred to sometimes collectively as HFA) is being evaluated. Being a better choice from the standpoint of preservation of the ozonosphere, HFA has the drawback that the dispersants (e.g. soybean lecithin) heretofore used in combination with CFC are not soluble in HFA at all, with the result that compound (A) cannot be dispersed in HFA and, hence, no satisfactory aerosol product of compound (A) can be provided.